Chronic metformin administration was found to ameliorate synaptic malfunctions and cognitive impairment in the amyloid precursor protein (APP)swe/presenilin-1(PS1)DE9 (APP/PS1) mouse model of AD via the inhibition of cyclin-dependent kinase 5 (Cdk5) activity [49]. This evidence concerns the gene PSEN1 and Alzheimer disease.